Many of the mechanisms that underlie receptor-mediated endocytosis and the internalization of macromolecules from the cell surface or the extracellular space through coated pits were elucidated through analysis of the LDL receptor (LDLR). It is now clear that the LDLR is one member of a larger family of cell surface receptors that share the same overall structural organization, which is defined by the ordered arrangement of several conserved functional motifs (Figure 1). Although many members of this family interact with lipoproteins and other ligands related to lipid metabolism, most (with the exception of the LDLR) also bind ligands that are unrelated to lipid metabolism (1). Knockout experiments in mice suggest that LDLR family members are involved in cellular signal transduction events such as the transport of hormones and vitamins and the activation or modulation of cellular kinases, as shown by recent work from our lab and that of others (2, 3).